Dominant C2 domain epitope specificity of inhibitor antibodies elicited by a heat pasteurized product, factor VIII CPS-P, in previously treated hemophilia A patients without inhibitors.
From June, 1990, to November, 1991, in The Netherlands and Belgium, 16 previously treated severe hemophilia A patients (PTP) developed inhibitors after exposure to factor VIII CPS-P, a new heat pasteurized product. A previously untreated patient (PUP) also developed an inhibitor to CPS-P. In inhibitor neutralization assays with recombinant fVIII C2 and A2 domain polypeptides, plasmas from 14 PTPs were > or = 79% neutralized by C2 and < 10% by A2, but the PUP plasma was partially neutralized by C2 (48%) and A2 (28%). Immunoprecipitation assays of the PTP and PUP plasmas with the fVIII heavy chain and with recombinant C2 and A3-C1 polypeptides confirmed that the C2 dominant immune response to CPS-P was found only in the PTPs. Competition of the binding of 2 inhibitors to 125I-CPS-P by unlabeled CPS-P and another plasma fVIII was similar, demonstrating that the antibody response was not directed to epitopes only present in CPS-P. We propose that the immunogenicity of the CPS-P C2 domain was altered by heat pasteurization.
Sawamoto
Y
Y
American Red Cross, Rockville, MD 20855, USA.
Prescott
R
R
Zhong
D
D
Saenko
E L
EL
Mauser-Bunschoten
E
E
Peerlinck
K
K
van den Berg
M
M
Scandella
D
D
D000293:Adolescent; D000328:Adult; D000937:Antigen-Antibody Reactions; D002648:Child; D002675:Child, Preschool; D000939:Epitopes; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000188:drug therapy / Q000276:immunology*; D006358:Hot Temperature; D006801:Humans; D016056:Immunodominant Epitopes; D008875:Middle Aged; D017434:Protein Structure, Tertiary; D013242:Sterilization
D000939:Epitopes; D016056:Immunodominant Epitopes; D005169:Factor VIII